A Guide to Living with Myasthenia Gravis  Patients

Myasthenia Gravis?

Muscle weakness and exhaustion characterize the chronic autoimmune neuromuscular disease myasthenia gravis (MG). Most affected are the skeletal muscles that move bones. M. gravis is incurable. However, medicines can reduce symptoms, allowing individuals with the illness to live reasonably normal lives. Most myasthenia gravis patients live normal lives.

The main cause of myasthenia gravis?

Antibodies to the acetylcholine receptor are the most common cause; however, antibodies to other proteins like MuSK can also disrupt neuromuscular junction communication. The thymus gland affects immunity and may be linked to myasthenia gravis.

The 5 stages of myasthenia gravis?

• M. gravis phases
• Class I: Eye-only muscular weakening.
• Class II: Mild muscle weakness.
• Class III: Moderate muscle weakness.
• Class IV: Severe muscle weakness.
• Class V: Severe muscle weakness inhibits breathing. Intubation or mechanical ventilation may be needed.

End-stage myasthenia gravis?

Respiratory issues, renal failure, and muscle weakness are symptoms of end-stage myasthenia gravis. Patient support may require long-term mechanical ventilation.

Treatment for M. gravis

Acetylcholinesterase inhibitors like pyridostigmine improve nerve-muscle signals, and immunosuppressants like corticosteroids and azathioprine reduce the immune system's attack on the body's acetylcholine receptors to control muscle weakness in myasthenia gravis. Thymectomy can alleviate symptoms, while plasma exchange and IVIG are utilized for severe patients or crises.

M.gravida symptoms

• Activity worsens symptoms, whereas rest improves them.
• Gradual or abrupt onset and vast severity vary.
• Within 1–2 years of illness start, symptoms peak.

Ocular Myasthenia

• Often first signs:
• Ptosis: Eyelid drooping
• Diplopia: Horizontal or vertical double vision, usually better with one eye closed.
• Ophthalmoparesis: Semi-paralysis of eye motions

Facial/Throat Muscles

• Influences speaking, swallowing, and expression:
• Speech softness, nasality, or slur
• Dysphagia: Choking or nasal regurgitation of drinks; difficulty swallowing
• Chewing fatigue: Especially with difficult foods
• Flat, limited expressions: Having trouble smiling or lifting eyebrows

Limb and Neck Muscles

• Possible late disease progression:
• Weak neck: Trouble holding head up
• Weak arms and legs: Having trouble lifting, climbing, or walking
• Repetitive movement fatigue: Exercise worsens symptoms.

Severe respiratory muscles

• Shortness of breath: dyspnea
• Myasthenic crisis: Critical respiratory failure needing emergency care

Autoantibody-Mediated Mechanisms

• Most common acetylcholine receptor (AChR) antibodies inhibit or kill receptors on muscle cells, limiting signal transmission.
• In some cases, Muscle-Specific Kinase (MuSK) Antibodies impair AChR clustering at the neuromuscular junction.
• LRP4 and Agrin Antibodies: Rare yet linked to synaptic impairment.

Thyroid Disorders

• Thymic hyperplasia: Contributes to autoantibody production in 70-80% of instances.
• Thymomas: Tumors of the thymus, detected in ~10-15% of MG patients, are generally linked to severe illness.

Brief Neonatal MG

Maternal AChR antibodies pass through the placenta, causing brief neonatal MG, which subsides within weeks.

Risk and demographic factors

• Bimodal age distribution
• Women: Usually <40 years
• Men: Usually over 60
• Females are more likely to have early-onset MG than males.

Genotype Susceptibility

• HLA-B8, HLA-DR3 may increase risks.
• A Family History: Rarely, autoimmune disorders cluster familially.

Environment Triggers

• Infections like EBV and CMV can cause immunological dysregulation.
• Medications: Drugs can worsen MG or reveal dormant symptoms:
• Beta-blockers
• Fluoroquinolones
• Sulfate magnesium
• Penicillamine

Hormonal Effects

• Gender disparities in disease onset and severity may be due to estrogen fluctuations.
• Autoimmune Mechanism: AChR, MuSK, and LRP4 antibodies impede neuromuscular transmission.
• Thymus Abnormalities: Thymoma or hyperplasia produces autoantibodies.
• Genetics: HLA-B8, HLA-DR3; uncommon family instances
• Environmental triggers: viruses, drugs
• Age and gender: Women <40, Men >60
• Estrogen may affect immunity.
• Antibodies from mothers cross the placenta.

Diagnose Myasthenia Gravis?

• Clinical Assessment
• A Neurological Exam
• Strength and tone
• Reflexes
• Balance and coordination
• Eye and facial expressions
• Repeated use worsens symptoms.

Serology tests

• Autoantibody detection
• AChR: 80-85%: Most prevalent; validates diagnosis.
• MuSK ~5–10%: Found in seronegative MG.
• LRP4: Rare emerging marking; scarce.
• Note: Ocular MG patients may test negative for all antibodies.

Electrodiagnosis Analysis

• Using Repetitive Nerve activation (RNS), muscle action potentials decrease with repeated activation.

Single-Fiber Electromyography

• Single-Fiber Electromyography is highly sensitive and detects abnormalities in single-fiber neuromuscular transmission.
• Pharmacological Tests
• Tensilon (Edrophonium) Test
• Acetylcholinesterase short-acting inhibitor
• Temporary muscular strength (particularly ocular) improvement supports MG diagnosis
• Cardiovascular monitoring needed due to adverse effects

Bedside Tests: Ice Pack

• Apply it to drooping eyelids for 2 minutes.
• Improvement suggests MG (cooling improves neuromuscular transmission).

Imaging Exams

• Chest CT or MRI evaluates thymic abnormalities (hyperplasia or thymoma).

Lung Function Tests

• Investigates respiratory muscle involvement in probable myasthenic crises.
• Summary Flowchart
• Clinical suspicion of variable weakness
• Neurological + ice pack test
• Antibody testing for AChR and MuSK
• RNS, SFEMG electrodiagnostics
• Edrophonium test (if needed)
• Diagnostic thymus imaging
• Severe pulmonary tests

Medicines for Myasthenia Gravis

• Treatment Goals
• Improve neuromuscular transmission
• Stop autoimmunity
• Prevent myasthenic crises
• Boost life quality

Also, read https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/myasthenia-gravis

Medication Categories: 

1. Acetylcholinesterase Inhibitors

• Increase acetylcholine to improve nerve-muscle communication.
• Pyridostigmine (Mestinon®): First-line symptom management
• Neostigmine: Rarely used
• Rapid onset without illness progression control

2. Corticosteroids

• Reduce immunological response and antibody generation.
• For mild to severe MG, prednisone is administered.
• Weight gain, mood swings, osteoporosis, glucose intolerance

3. Anti-steroid immunosuppressants

• When steroids are not advised or for long-term control.
• Imuran® (azathioprine)
• CellCept® mycophenolate mofetil
• Tacrolimus - Cyclosporine
• Monitor liver, kidney, and blood parameters regularly.

4. Biologic Therapy Targets

• For refractory or antibody-specific MG, use Rituximab on B-cells. MuSK-positive MG
• Efgartigimod (Vyvgart®): Neonatal AChR-positive Fc receptor MG
• Rystiggo®: FcRn AChR-positive MG
• Nipocalimab (IMAAVY®): FcRn. Emerging choice
• Eculizumab (Soliris®) Complement C5. Refractory MG generally
• Unomiris® (ravulizumab): C5 complement. Extended-acting alternative

Acute Exacerbation Rescue Therapies

• Intravenous immunoglobulin (IVIg) temporarily suppresses dangerous antibodies.
• Crisis or pre-op preparation
• Autoantibodies are removed using Plasma Exchange (PLEX).
• Quick relief for severe symptoms

Surgical Choice

• Thymectomy
• Recommended for thymoma or generalized MG patients under 60.
• May cause remission or lower medication needs

Lifestyle and Support

• Energy pacing: Avoid overwork
• Nutrition: Dysphagia-friendly Soft foods
• Stress management: Lowers flare-ups
• Avoid live vaccinations during immunosuppression.

Which myasthenia gravis treatment works best?

The video explains the treatment option for Myasthenia Gravis

• Personalized therapy strategies are superior to universal solutions for Myasthenia Gravis (MG), as factors such as the type, severity, autoantibody profile, and response dictate the most effective treatment. Following consensus principles, here's an organized presentation of the best possibilities.
• First-Line Symptom Treatment
• Mestinon® (pyridostigmine)
• Therapy for immunosuppression
• Steroid-sparing agents: Prednisone

PLEX and IVIg are rescue therapies.

• Myasthenic crises, fast alleviation
• Pros: Rapid
• Cons: Brief, resource-intensive

Surgical Choice

• Thymectomy
• Indication: Thymoma or widespread MG in patients <60 years.
• Remission or medication reduction may occur.

Supportive Care

• Energy pacing, stress reduction
• Dysphagia diet alterations
• Avoid fluoroquinolones and beta-blockers that worsen MG.

Conclusion, 

Personalized therapy can help manage MG, even though it cannot be cured. Multimodal diagnosis: Targeted medicines and improved diagnostic methods allow MG patients to live active, satisfying lives. Knowledge of a condition improves self-management, adherence, and resilience.